Chronic Myeloid Leukaemia

Proliferation of myeloid cells - granulocytes and their precursors, other lineages (platelets)

Aetiology

  • Philadelphia chromosome, it is a t(9:22) translocation
    • Results in a new gene - BCR-ABL1
    • Produces p210 tyrosine kinase. Leads to:
      • Increased proliferation
      • Reduced apoptosis
      • Genomic instability → disease progression
  • Predominantly adults (40–60 years)
  • Slight male predominance
  • Rare in children

Pathophysiology

Three typical phases, the chronic phase, the accelerated phase and the blast phase:
  • The chronic phase can last around 5 years, is often asymptomatic and patients are diagnosed incidentally with a raised white cell count
  • The accelerated phase occurs where the abnormal blast cells take up a high proportion of the cells in the bone marrow and blood (10-20%)
    • In the accelerated phase patients become more symptomatic, develop anaemia and thrombocytopenia and become immunocompromised
  • The blast phase follows the accelerated phase and involves an even high proportion of blast cells (>30%)
    • This phase has severe symptoms and pancytopenia
    • It is often fatal

Clinical Pesentation

Clinical Phases

Phase
Blast % (BM or PB)
Key Features
Chronic phase
<10%
Often asymptomatic, splenomegaly
Accelerated phase
10–19%
Worsening cytopenias, splenomegaly
Blast crisis
≥20%
Acute leukemia–like (AML or ALL)

Clinical Features

Chronic Phase
  • Fatigue, weight loss
  • Early satiety
  • Massive splenomegaly
  • Night sweats
  • Sometimes asymptomatic (incidental CBC)
Accelerated / Blast Phase
  • Fever, infections
  • Bleeding
  • Bone pain
  • Rapid spleen enlargement

Investigations

Complete Blood Count

Parameter
Finding
WBC
Markedly ↑ (often >100,000/µL)
Differential
Left shift (myelocytes, metamyelocytes)
Basophils
↑ (characteristic)
Eosinophils
↑
Platelets
Normal or ↑ (↓ in late disease)
Hemoglobin
Mild–moderate ↓
📌 Basophilia + very high WBC = strong clue for CML
 

Peripheral Blood Smear

Feature
Description
Myeloid precursors
All stages present
Blasts
<10% (chronic phase)
Basophils
Increased
Platelets
Large, abnormal forms
notion image

Bone Marrow

  • Hypercellular
  • Myeloid hyperplasia
  • Increased M:E ratio
  • Small megakaryocytes (hypolobated)

Management

  • Fatal without stem cell/bone marrow transplant in the chronic phase
  • Durable treatment responses with tyrosine kinase inhibitors e.g. imatinib
    • Prevents the action of the BCR-ABL fusion protein i.e.this is the abnormal protein produced by the Ph mutation